Site Navigation

Site Mobile Navigation

Monkey Born With Genetically Engineered Cells

Scientists in Portland, Ore., report that they have inserted a foreign gene into a monkey egg, fertilized the egg and produced a baby monkey with the added gene in its cells.

The scientists say they believe that this is the first time researchers have used techniques of genetic engineering to alter an unfertilized egg of a primate, intending that the change be passed on to future generations.

The gene, which comes from a jellyfish, is only a marker -- it causes cells to make a protein that glows under a fluorescent light. And in this case, though the monkey's cells have the gene, they are not making the protein, the researchers report. Further, it is too soon to tell whether the monkey's sperm will contain the added gene.

''In many ways this is an incremental step,'' said Dr. Gerald Schatten, the senior author of the report, published today in the journal Science. Dr. Schatten is a professor of obstetrics and gynecology and cell and developmental biology at Oregon Health Sciences University.

''What is of interest, I think, in Gerry Schatten's work is the possibility that one could learn about certain types of diseases in ways that we really couldn't in humans,'' said Patricia Backlar, an ethicist at the university. ''But there's also the issue there that maybe we shouldn't do this on nonhuman primates. That's an issue. I can't resolve it for you.''

Dr. Schatten said his ultimate goal was to create colonies of monkeys that had been genetically modified to develop a human disease. Then, he said, he could use the animals to study new treatments for humans with the disease.

The evidence that the jellyfish gene got into the monkey's cells is purely molecular, Dr. Schatten said. Using an exquisitely sensitive method, polymerase chain reaction, he found the gene in cells from the monkey's cheek, hair, urine, placenta and cord blood. But none of those cells glowed with the fluorescent protein, he reported. And, he said, he does not yet know whether the gene will be in the monkey's sperm cells, a necessity if he is to use genetically modified monkeys to produce a monkey colony.

Prof. Lori B. Andrews of the Chicago-Kent College of Law, who studies new reproductive technologies, said she worried about what the experiment might mean for the future of genetic manipulations in people.

There is widespread agreement that genetically modified mice long used in research on human diseases have serious limitations.

Dr. Richard Tasca, who is program director in the reproductive sciences branch of the National Institute of Child Health and Human Development, said those limitations were behind the National Institutes of Health's decision to finance the research. With some diseases, Dr. Tasca said, ''a mouse is not close enough to a human.''

Some researchers noted the preliminary nature of the Oregon work.

''It's got the DNA in there, so its a transgenic animal,'' said Dr. Brigid Hogan, a professor of cell biology at Vanderbilt University Medical Center and an investigator with the Howard Medical Institute. ''But unless you can show a high level of expression of the protein, it's not something you should be making a big fuss about and making extravagant claims about. I would be feeling very tentative about whether he had achieved the goals he had set out.''

Dr. Rudolph Jaenisch, a professor of biology at the Whitehead Institute at the Massachusetts Institute of Technology, said that the way Dr. Schatten inserted genes into the monkey eggs -- with a modified virus -- had been used for more than a quarter century in mice.

But, Dr. Jaenisch said, those experiments in mice and other animals also revealed the method's limitations. While the modified virus can get the genes into egg DNA, he said, the problem is that the genes are usually silenced and inactive, so that they do not direct cells to make proteins.

An error has occurred. Please try again later.

You are already subscribed to this email.

To make a monkey with a human disease, Dr. Jaenisch said, it is not enough just to get the gene into cells.

''You need whopping expression'' of the gene, he said, meaning that cells must make copious amount of the protein.

Moreover, he said, the method only allows for the creation of animals with added genes, while most human genetic diseases arise because a gene is missing or mutated.

''It is very unlikely from all we presently know about disease that there will be any breakthrough with this,'' Dr. Jaenisch said.

There are other ways to modify animals so that they have genes taken away or altered. Dr. Schatten said he was working on these as well.

Dr. Tasca said that to the best of his knowledge the research group headed by Dr. Schatten was the only one financed by the National Institutes of Health that is trying to modify monkeys genetically. The experiments are limited by the biology of the animals. It takes four to five years for a monkey to grow to sexual maturity, Dr. Schatten said, and a pregnancy lasts five and a half months.

In the current study, Dr. Schatten started with 224 monkey eggs, mixing them with a neutralized virus that carried the marker gene. The virus slipped into the eggs, taking the gene with it. The researchers ended up with 126 embryos. They selected 40 that looked most promising and those resulted in five pregnancies and the birth of three monkeys. One of them had the added gene, as determined by sensitive molecular assays.

Despite this limited success, Professor Andrews said she saw the experiment as essentially cracking open a door into a future world where genetic enhancement was sold by fertility clinics. She said she anticipated that many people would seize the chance to enhance their baby genetically, citing a recent poll in which 43 percent of couples who were asked said they would use genetic interventions to improve the physical capabilities of their child and 42 percent said they would want to upgrade their child's mental abilities.

Others were not so sure that the monkey experiment foretold human genetic engineering.

''There is nothing we have done that accelerates genetic modification in people,'' Dr. Schatten said. ''In many ways, the results should be sobering to renegades who think of extending this to humans. Let's say you want your kid on the basketball team. You can't take him to the coach and say, 'He has this growth gene in there but it's not expressed and he's not growing.' ''

Then there is the issue of the way the gene was inserted -- with a retrovirus, which can randomly insert genes into DNA and could potentially cause disease.

''If they're going to try genetic manipulations in humans, then they're certainly not going to use retroviruses,'' said Dr. Barry Zirkin, who is professor and head of the division of reproductive biology at Johns Hopkins University. ''It's too frightening to consider.''

''There may be a slippery slope somewhere,'' Dr. Zirkin said, ''but this can't be it.''

We are continually improving the quality of our text archives. Please send feedback, error reports,
and suggestions to archive_feedback@nytimes.com.

A version of this article appears in print on January 12, 2001, on Page A00001 of the National edition with the headline: Monkey Born With Genetically Engineered Cells. Order Reprints|Today's Paper|Subscribe